What are the benefits and risks of nicotinamide riboside (NR) supplementation in patients with Stickler syndrome?

Nicotinamide Riboside Supplementation in Stickler Syndrome: Benefits and Risks

There is currently insufficient evidence to recommend nicotinamide riboside (NR) supplementation specifically for patients with Stickler syndrome, as no clinical studies have evaluated its efficacy or safety in this genetic disorder.

Understanding Stickler Syndrome

Stickler syndrome is an inherited vitreoretinal and systemic disorder with the following key features:

• High myopia
• Retrolental, transvitreal, and epiretinal membranes and strands
• Chorioretinal pigment alterations
• Lattice degeneration, often with perivascular component extending posteriorly
• Various other abnormalities including glaucoma and cataract
• Systemic features including skeletal dysplasia, flattened facies, high arched or cleft palate, hearing loss 1

Stickler syndrome is associated with an increased risk of rhegmatogenous retinal detachment (RRD), with perivascular lattice degeneration being frequently observed 1.

NAD+ and Nicotinamide Riboside

Nicotinamide riboside (NR) is a precursor to nicotinamide adenine dinucleotide (NAD+), an essential coenzyme that:

• Plays a central role in mitochondrial energy metabolism
• Supports DNA repair mechanisms
• Maintains cellular redox status
• Functions as a cofactor for over 400 enzymes 2

Current Evidence on NR Supplementation

Potential Benefits

1. Mitochondrial Function: Long-term NR supplementation (5 months) has been shown to improve muscle mitochondrial number and myoblast differentiation in humans 3.

2. NAD+ Metabolism: NR effectively stimulates NAD+ metabolism in healthy middle-aged and older adults 4.

3. Inflammatory Reduction: NR may play a role in reducing inflammatory states 5.

Limitations and Concerns

1. Limited Clinical Evidence: Despite promising preclinical results, oral NR supplementation has shown few clinically relevant effects in humans 5.

2. Potential Risks: Raising NAD+ levels may lead to:

   • Accumulation of toxic metabolites
   • Theoretical risk of tumorigenesis
   • Promotion of cellular senescence 2

3. Lack of Disease-Specific Studies: No studies have evaluated NR in Stickler syndrome specifically.

Recommendations for Patients with Stickler Syndrome

Nutritional Approach

Rather than NR supplementation, focus on adequate niacin intake through diet:

• Daily recommended intake: 16 mg/day for men, 14 mg/day for women
• Excellent sources: meat, poultry, fish
• Moderate sources: nuts, legumes, whole grains 2

Monitoring and Management

For Stickler syndrome patients, prioritize:

1. Regular ophthalmologic evaluation to monitor for:

   • Retinal breaks
   • Lattice degeneration
   • Early signs of retinal detachment 1

2. Prompt treatment of any retinal tears using laser demarcation or cryotherapy 1

3. Genetic counseling for family planning, as Stickler syndrome follows an autosomal dominant inheritance pattern 1

Conclusion

While NR shows promise for improving mitochondrial function and NAD+ metabolism in general populations, there is no evidence to support its use specifically for Stickler syndrome. Patients should focus on established management strategies for Stickler syndrome and maintain adequate niacin intake through dietary sources rather than NR supplementation.

If considering NR supplementation for general health purposes (not specifically for Stickler syndrome), patients should be aware that:

• Safety appears relatively favorable in short-term studies
• Upper limits for nicotinamide intake are approximately 900 mg/day for adults
• Clinical benefits remain limited despite promising preclinical results 2, 5

Any supplementation decision should be made with awareness of the limited clinical evidence supporting NR's efficacy for specific health conditions.